Molecular homing and retention of muscle membrane stabilizing copolymers by non-invasive optical imaging in vivo
First-in-class membrane stabilizer Poloxamer 188 (P188) has been shown to confer membrane protection in an extensive range of clinical conditions; however, elements of the systemic distribution and localization of P188 at the organ, tissue, and muscle fiber levels in vivo have not yet been elucidate...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050122001784 |
| _version_ | 1828070654119772160 |
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| author | Addeli Bez Batti Angulski Houda Cohen Mihee Kim Dongwoo Hahn Nicholas Van Zee Timothy P. Lodge Marc A. Hillmyer Benjamin J. Hackel Frank S. Bates Joseph M. Metzger |
| author_facet | Addeli Bez Batti Angulski Houda Cohen Mihee Kim Dongwoo Hahn Nicholas Van Zee Timothy P. Lodge Marc A. Hillmyer Benjamin J. Hackel Frank S. Bates Joseph M. Metzger |
| author_sort | Addeli Bez Batti Angulski |
| collection | DOAJ |
| description | First-in-class membrane stabilizer Poloxamer 188 (P188) has been shown to confer membrane protection in an extensive range of clinical conditions; however, elements of the systemic distribution and localization of P188 at the organ, tissue, and muscle fiber levels in vivo have not yet been elucidated. Here we used non-invasive fluorescence imaging to directly visualize and track the distribution and localization of P188 in vivo. The results demonstrated that the Alx647 probe did not alter the fundamental properties of P188 to protect biological membranes. Distribution kinetics in mdx mice demonstrated that Alx647 did not interface with muscle membranes and had fast clearance kinetics. In contrast, the distribution kinetics for P188-Alx647 was significantly slower, indicating a dramatic depot and retention effect of P188. Results further demonstrated the significant retention of P188-Alx647 in the skeletal muscle of mdx mice, showing a significant genotype effect with a higher fluorescence signal in the mdx muscles over BL10 mice. High-resolution optical imaging provided direct evidence of P188 surrounding the sarcolemma of skeletal and cardiac muscle cells. Taken together, these findings provide direct evidence of muscle-disease-dependent molecular homing and retention of synthetic copolymers in striated muscles thereby facilitating advanced studies of copolymer-membrane association in health and disease. |
| first_indexed | 2024-04-11T00:42:20Z |
| format | Article |
| id | doaj.art-3a1e938556b44502a67ac72b87b2ecd7 |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-04-11T00:42:20Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-3a1e938556b44502a67ac72b87b2ecd72023-01-06T04:17:10ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012023-03-0128162176Molecular homing and retention of muscle membrane stabilizing copolymers by non-invasive optical imaging in vivoAddeli Bez Batti Angulski0Houda Cohen1Mihee Kim2Dongwoo Hahn3Nicholas Van Zee4Timothy P. Lodge5Marc A. Hillmyer6Benjamin J. Hackel7Frank S. Bates8Joseph M. Metzger9Department of Integrative Biology and Physiology, University of Minnesota Medical School, 6-125 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USADepartment of Integrative Biology and Physiology, University of Minnesota Medical School, 6-125 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USADepartment of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, USADepartment of Integrative Biology and Physiology, University of Minnesota Medical School, 6-125 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USADepartment of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, USADepartment of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, USA; Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USADepartment of Chemistry, University of Minnesota, Minneapolis, MN 55455, USADepartment of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, USA; Corresponding author Benjamin J. Hackel, Department of Chemical Engineering and Materials Science, University of Minnesota, 356 Amundsun Hall, Minneapolis, MN 55455, USA.Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, USADepartment of Integrative Biology and Physiology, University of Minnesota Medical School, 6-125 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USA; Corresponding author Joseph M. Metzger, Department of Integrative Biology & Physiology, University of Minnesota Medical School, 6-125 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USA.First-in-class membrane stabilizer Poloxamer 188 (P188) has been shown to confer membrane protection in an extensive range of clinical conditions; however, elements of the systemic distribution and localization of P188 at the organ, tissue, and muscle fiber levels in vivo have not yet been elucidated. Here we used non-invasive fluorescence imaging to directly visualize and track the distribution and localization of P188 in vivo. The results demonstrated that the Alx647 probe did not alter the fundamental properties of P188 to protect biological membranes. Distribution kinetics in mdx mice demonstrated that Alx647 did not interface with muscle membranes and had fast clearance kinetics. In contrast, the distribution kinetics for P188-Alx647 was significantly slower, indicating a dramatic depot and retention effect of P188. Results further demonstrated the significant retention of P188-Alx647 in the skeletal muscle of mdx mice, showing a significant genotype effect with a higher fluorescence signal in the mdx muscles over BL10 mice. High-resolution optical imaging provided direct evidence of P188 surrounding the sarcolemma of skeletal and cardiac muscle cells. Taken together, these findings provide direct evidence of muscle-disease-dependent molecular homing and retention of synthetic copolymers in striated muscles thereby facilitating advanced studies of copolymer-membrane association in health and disease.http://www.sciencedirect.com/science/article/pii/S2329050122001784synthetic block copolymersPoloxamer 188membrane stabilizerDuchenne muscular dystrophydystrophin-deficient mdx micedamaged muscle membrane |
| spellingShingle | Addeli Bez Batti Angulski Houda Cohen Mihee Kim Dongwoo Hahn Nicholas Van Zee Timothy P. Lodge Marc A. Hillmyer Benjamin J. Hackel Frank S. Bates Joseph M. Metzger Molecular homing and retention of muscle membrane stabilizing copolymers by non-invasive optical imaging in vivo Molecular Therapy: Methods & Clinical Development synthetic block copolymers Poloxamer 188 membrane stabilizer Duchenne muscular dystrophy dystrophin-deficient mdx mice damaged muscle membrane |
| title | Molecular homing and retention of muscle membrane stabilizing copolymers by non-invasive optical imaging in vivo |
| title_full | Molecular homing and retention of muscle membrane stabilizing copolymers by non-invasive optical imaging in vivo |
| title_fullStr | Molecular homing and retention of muscle membrane stabilizing copolymers by non-invasive optical imaging in vivo |
| title_full_unstemmed | Molecular homing and retention of muscle membrane stabilizing copolymers by non-invasive optical imaging in vivo |
| title_short | Molecular homing and retention of muscle membrane stabilizing copolymers by non-invasive optical imaging in vivo |
| title_sort | molecular homing and retention of muscle membrane stabilizing copolymers by non invasive optical imaging in vivo |
| topic | synthetic block copolymers Poloxamer 188 membrane stabilizer Duchenne muscular dystrophy dystrophin-deficient mdx mice damaged muscle membrane |
| url | http://www.sciencedirect.com/science/article/pii/S2329050122001784 |
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